Reaction mechanism of isoflavone O-methyltransferase: A theoretical investigation

The methyl-transfer reaction mechanism catalyzed by Isoflavone O-methyl-transferase (IOMT) and the roles of several residues around the active site are investigated by employing density functional method. The calculations confirm that the proton transfer from daidzein to His257 occurs barrierlessly, and the methyl group is transferred from S-adenosyl-l-methionine (SAM) to phenolate ion in a single S N 2 step with a barrier of 17.0 kcal/mol, consistent with experimental value. Glu318 and Asp288 play important roles in lowering the reaction barrier.